DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
2. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 03 November 2025 has been entered.
3. Applicant's arguments and amendments to the claims presented in the reply of 03 November 2025 have been fully considered but do not place the application in condition for allowance. All rejections and objections not reiterated herein are hereby withdrawn.
Claim Status
4. Claims 1-10 are pending.
Claims 3-9 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1, 2 and 10 have been examined herein.
It is noted that in the reply of 13 February 2025, Applicant elected the species of the biomarker of NONHSAT006501.2. In the reply of 03 November 2025, Applicant amended the claims so that the claimed kits comprise primers or probes for each of the NONHSAT006501.2, NONHSAT071649, FAM25A, and CRCT1 biomarkers. Accordingly, the elected species is now considered to be limited to the combination of each of the NONHSAT006501.2, NONHSAT071649, FAM25A, and CRCT1 biomarkers.
Claim Interpretation
5. The claims recite that the kit comprises “a label selected from the group consisting of a fluorescent label, a radioisotope label, or an enzymatic label, wherein the label is conjugated directly or indirectly to the probes or primers for detection of the four biomarkers.” The claims have been interpreted as requiring that each primer or probe in the kit (configured to detect each of the four biomarkers) is conjugated directly or indirectly to a fluorescent label, a radioisotope label, or an enzymatic label. That is, the claims do not encompass kits in which one or more of the primers or probes configured to detect the four biomarkers is not conjugated to a fluorescent label, a radioisotope label, or an enzymatic label.
In view of the amendment to the claims, the claims no longer recite the judicial exception of a product of nature and are patent-eligible under 35 U.S.C. 101.
New Claim Rejections - 35 USC § 112(a) - New Matter
6. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 2 and 10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
In the reply of 03 November 2025, the claims were amended to recite that “the kit is configured to achieve a diagnostic performance of at least 0.91 area under the curve (AUC), 71% sensitivity, and 100% specificity.”
The disclosure as originally filed does not provide basis for the broadly claimed kit configured to achieve a diagnostic performance (for the detection of anything) of at least 0.91 area under the curve (AUC), 71% sensitivity, and 100% specificity.
The specification at page 39, lines 13-15 states:
"A panel of four of the eight salivary exRNAs [NONHSAT006501.2; NONHSAT071649; FAM25A; NM_019060] can detect gingivitis with a clinical performance of 0.91 AUC (area under the curve) with 71% sensitivity and 100% specificity."
Similarly, p. 43, lines 6-11 states:
"Linear regression analysis of 8 validated exRNAs revealed that four exRNA marker model [NONHSAT006501.2 (m1), NONHSAT071649 (m2), NM_001146157 (m7), NM_019060 (m10)] could potentially provide a discriminatory performance of 0.91 AUC (area under the curve) with 71% sensitivity and 100% specificity (FIG. 4)."
Thus, the specification provides support only for the concept that the detection assays disclosed therein in which the combination of all 4 of the RNA biomarkers of NONHSAT006501.2 (m1), NONHSAT071649 (m2), FAM25A and CRCT1 were detected in a saliva sample using particular primers or probes provided a diagnostic performance for the detection of gingivitis of 0.91 AUC with 71% sensitivity and 100% specificity.
The specification does not teach the concept of a kit having the recited diagnostic performance (for diagnosing gingivitis or for any other unstated condition). There is no basis in the disclosure for the concept of a kit comprising any probes or primers for the detection of NONHSAT006501.2, NONHSAT071649, FAM25A and CRCT1 conjugated to a fluorescent, radioactive or enzymatic label and instructions, is configured so that the kit itself has the property of being able to achieve a diagnostic performance of at least 0.91 area under the curve (AUC), 71% sensitivity, and 100% specificity.
New Claim Rejections - 35 USC § 112(b) - Indefiniteness
7. The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 2 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 2 is indefinite over the recitation of “the detection of the four biomarkers is performed by” because “the detection” lacks proper antecedent basis. While the claim previously refers to a reagent configured to detect the four biomarkers, the claim does not previously refer to “the detection” of the four biomarkers. it is not clear as to how this limitation is intended to further limit the claimed kits. The claims are drawn to a product and not a method of using or detecting the product. While it is clear as to what meant by a method for detecting the four biomarkers comprising performing reverse transcription, etc. and what is meant by a primer or probe for performing reverse transcription etc., it is not clear as to how defining how the biomarkers are to be detected further limits the kit comprising primers or probes for the four biomarkers.
New Claim Rejections - 35 USC § 103
8. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 2 and 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Affymetrix. Datasheet. “GeneChip® Human Transcriptome Array 2.0” July 2013; cited in the IDS of 04/15/2024) in view of Lorenz (U.S. Patent No. 6706867) and Ahern, H. (The Scientist. July 1995. 9(15): 20-25; cited in the IDS of 04/15/2024), as evidenced by the present specification at p. 40, lines 15-23 and p. 42, lines 14-22.
Affymetrix teaches GeneChip® Human Transcriptome Array 2.0 (HTA 2.0) which comprises probes for detecting each of the biomarkers of NONHSAT006501.2, NONHSAT071649, FAM25A, and CRCT1. The fact that HTA 2.0 comprises probes that specifically detect NONHSAT006501.2, NONHSAT071649, FAM25A, and CRCT1 nucleic acids is evidenced by the teachings in the specification (at p. 40, lines 15-23 and p. 42, lines 14-22) wherein it is disclosed that the saliva samples were profiled using the GeneChip® Human Transcriptome Array 2.0 expression arrays to identify RNAs whose expression level was correlated with gingivitis and 10 exRNA biomarkers were identified including NONHSAT006501.2, NONHSAT071649, FAM25A (NM_001146157), and CRCT1 (NM_019060). Note that the present specification is cited only to establish what is inherent to the Affymetrix GeneChip® Human Transcriptome Array 2.0.
Note also that the present claims recite the open claim language of “comprising” and thereby may include any number of additional probes of any identity.
Affymetrix does not teach labeling the probes that are immobilized onto the array.
However, Lorenz (col. 3, lines 45-65; col. 12, lines 10-28; col. 18, lines 7-19) teaches compositions comprising arrays having immobilized probes. Lorenz (col. 12, lines 10-28; col. 24, lines 49-61)) teaches labeling the probes with a detectable moiety, including fluorescent, radioactive and enzyme moieties.
In view of the teachings of Lorenz, it would have been obvious to one of ordinary skill in the art at the time the invention was made to have modified the arrays of Affymetrix so as to have labeled the immobilized probes with a detectable moiety, such as biotin, a radioisotope, an enzyme, a fluorescent substance or a luminescent substance, in order to have facilitated the detection of target nucleic acids which hybridize to the immobilized probes.
Affymetrix teaches that the GeneChip® Human Transcriptome Array 2.0 is available in kit form including additional reagents for performing microarray reactions (see p. 2 “Ordering information”).
Affymetrix does not specifically teach that the kit further comprises instructions for use.
However, reagent kits comprising instructions for performing DNA detection assays were conventional in the diagnostic arts before the effective filing date of the claimed invention. In particular, Ahern discloses the general concept of kits for performing detection methods and discloses that kits provide the advantage of pre-assembling the specific reagents required to perform an assay and ensure the quality and compatibility of the reagents to be used in the assay. Ahern (page 22) teaches that kits also provide the benefits of cost-effectiveness and time efficiency. Ahern teaches that an additional advantage of kits is that they include instructions detailing how to use the reagents in the kit.
Accordingly, in view of the conventionality in the analytical arts of including instructions in kits, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have included instructions in the kit of Affymetrix for the advantage of providing the practioner with information as to how to use the components of the kit.
With respect to the printed material in the instructions, Applicant’s attention is directed to MPEP 2111.05:
“To be given patentable weight, the printed matter and associated product must be in a functional relationship. A functional relationship can be found where the printed matter performs some function with respect to the product to which it is associated. See Lowry, 32 F.3d at 1584, 32 USPQ2d at 1035 (citing Gulack, 703 F.2d at 1386, 217 USPQ at 404). …
B. Evidence Against a Functional Relationship
Where a product merely serves as a support for printed matter, no functional relationship exists. These situations may arise where the claim as a whole is directed towards conveying a message or meaning to a human reader independent of the supporting product.”
MPEP 2111.05 also states:
“where the printed matter and product do not depend upon each other, no functional relationship exists. For example, in a kit containing a set of chemicals and a printed set of instructions for using the chemicals, the instructions are not related to that particular set of chemicals. In re Ngai, 367 F.3d at 1339, 70 USPQ2d at 1864.”
In the present situation, the instructions do not physically or chemically affect the other components in the kit and the instructions do not have a functional relationship with the other components in the kit. Thereby, the instructions in the claimed kits are considered to comprise any instructions and do not materially distinguish the claimed kits with instructions over the kits suggested by the combined teachings of Affymetrix, Lorenz and Ahern.
Regarding the preamble of the present claims, as set forth in MPEP 2111.02 II: “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction.” Herein, the preamble language of “for detecting gingivitis in a subject” is a statement of purpose and intended result and does not materially affect the structural properties of the kit or its components. Thereby, the intended use of the kits does not materially distinguish the claimed kits over the kits and compositions suggested by the teachings of Affymetrix.
Regarding the recitation that the kit is configured to achieve a diagnostic performance of at least 0.91 AUC (area under the curve) with 71% sensitivity and 100% specificity, the modified kit of Affymetrix as set forth above is considered to have this property, absence evidence to the contrary. The probes present on the Affymetrix HTA 2.0 microarray are the same as those used in the present application. The present claims do not recite any structural limitations for the probes or primers which would distinguish the probes or primers over those present on the modified array of Affymetrix. The claims encompass kits comprising any probe or primer of any sequence “configured to detect” NONHSAT006501.2, NONHSAT071649, FAM25A, and CRCT1, wherein the probe or primer comprises any fluorescent label, a radioisotope label, or an enzymatic label. Modification of HTA 2.0 so as to have labeled the probes with, for example, a fluorescent, radioactive or enzymatic label as taught by Lorenz would have also resulted in a kit “configured to detect” (i.e., which detects) NONHSAT006501.2, NONHSAT071649, FAM25A, and CRCT1, wherein the probe comprises any fluorescent label, a radioisotope label, or an enzymatic label. The claims do not recite any specific structural features of the probes which materially distinguishes the claimed probes and kits over those suggested by the combined prior art.
Regarding claim 2, Affymetrix teaches that the kits comprising the GeneChip® Human Transcriptome Array 2.0 is to be used for microarray analysis.
Regarding claim 10, since the probes are on a microarray, they are configured to be used for the detection of NONHSAT006501.2, NONHSAT071649, FAM25A, and CRCT1 in a single reaction.
Response to Remarks:
The response traversed the prior rejections by stating that the claims have been amended to recite a kit comprising a reagent set with probes or primers configured to detect each of the biomarkers of NONHSAT006501.2, NONHSAT071649, FAM25A, and CRCT1 in a saliva sample from a subject. It is argued that the cited prior art does not disclose a kit containing probes or primers for all four of these specific biomarkers in combination.
A new grounds of rejection has now been applied to address the amendment to the claims to require that the kits comprise primers or probes for detecting each of the biomarkers of NONHSAT006501.2, NONHSAT071649, FAM25A, and CRCT1.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CARLA J MYERS whose telephone number is (571)272-0747. The examiner can normally be reached M-Th 6:30-5:00 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng (Winston) Shen can be reached on 571-272-0731. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CARLA J MYERS/Primary Examiner, Art Unit 1682